A mitochondrion is an organelle found in most eukaryotic cells. One of the major functions thereof is oxidative phosphorylation, through which energy derived from metabolism of a fuel material such as glucose or fatty acid is converted into adenosine triphosphate (ATP). ATP is used in driving various energy-requiring biosynthesis and other metabolic activities.
Structurally, the mitochondrion consists of an outer membrane and an inner membrane, and is a dynamic organelle continuously performing movement, fusion, and fission. The mitochondrion is organized in a tubular network, and mitochondrial morphology and number are precisely regulated by mitochondrial fusion-fission machinery. As proteins involved in mitochondrial fusion, mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), Opal, etc. are known, and Drp1, Fis1, etc. are known as proteins involved in mitochondrial fission.
Meanwhile, major constituents of the mitochondrion were discovered to play an important role in cell death, and thus, significance of mitochondria in cell death has been acknowledged since the 1990s. When cell death is induced, various proteins that regulate cell death, endoplasmic reticulum (ER), calcium ions present in cytoplasm, and other proteins related thereto move to the mitochondrion, and mitochondrial fission and fragmentation are caused by mitochondria-shaping protein. The fragmented mitochondrion loses membrane potential and its outer membrane becomes damaged, thereby increasing permeability of the outer membrane. Due to the increased permeability of the outer membrane, various proteins (e.g., cytochrome-C, etc.) in the mitochondrion are released to the cytoplasm through the outer membrane, and cause damage to the outer membrane, thereby increasing permeability thereof. As the permeability increases, various proteins (e.g., cytochrome-C, etc.) in the mitochondrion are released to the cytoplasm and at the same time, nuclei of the mitochondria agglutinate and mitochondrial DNA is cleaved. As a result, mitochondrial function is disabled, leading to cell death. Such mitochondria-mediated apoptosis has been widely observed, and in particular, is known to be implicated in pathogenesis of various degenerative diseases such as Parkinson's disease and hereditary optic neuropathy.
In this regard, research has been actively conducted on development of a formulation which can inhibit the mitochondrial damage for the purpose of preventing or treating a disease caused by the mitochondrial damage. For examples, Korean Laid-open Patent Application Nos. 2002-0042020 and 2014-0000733 disclose a dihydroxybenzaldehyde compound which effectively inhibits mitochondrial damage caused by a hydroxy radical and a pharmaceutical composition containing N-terminal Truncated Ubiquitin C-terminal hydrolase-L1 that has an important role in regulating stress inducing the mitochondrial damage as an active ingredient for the prevention and treatment of Parkinson's disease, respectively. Likewise, formulations regulating the mitochondrial damage have been developed, but the formulation development has been slow as it requires a tremendous investment of both time and money to confirm effects of the formulation on the mitochondrial damage. If a method that would enable effective discovery of various regulators of the mitochondrial damage is developed, it is predicted that a formulation for treating a disease caused by the mitochondrial damage can be more effectively developed.